The focus of this proposal is to develop strategies that permit the rapid and efficient transfer of HCMV specific immunity from donor to recipient resulting in protective immune responses that limit or prevent disease. This approach is based on the development of subunit vaccines containing isolated immunogenic viral proteins/peptides. Immunogenic peptides of HCMV pp65 and other HCMV proteins will be identified by a variety of techniques which are capable of inducing cell mediated and/or humoral responses in vitro and which point to their pan- dominance in a genetically outbred human population. HCMV proteins for potential inclusion in a vaccine will be prepared in large scale quantities using recombinant DNA technology. Analyses of cyanogen bromide digests of native and recombinant HCMV proteins will form the basis for determining peptide-specific immune reactivity. Candidate vaccines consisting of one or more purified proteins/peptides will be tested in the presence or absence of adjuvant in 20 normal adult volunteers, 10 seropositive and 10 seronegative. Vaccines which produce satisfactory results in normals will then be used to immunize bone marrow donors prior to transplantation. The results obtained are expected to provide information concerning the safety and utility of protein/peptide vaccines for HCMV and the ability to transfer boosted immunity by BMT. In addition, using prospectively determined pulmonary HCMV infection as an endpoint, the effect of transferred donor immunity on early virus reactivation and spread will be evaluated. These studies have broad implications for modulation of BMT recipient immunity by manipulation of the donor prior to transplantation, as well as for the general utility of protein vaccines in other groups of patients susceptible to severe HCMV-related disease.